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1.
Carbohydr Polym ; 225: 115160, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521318

RESUMO

Hydrogels with good mechanical properties are promising for various applications. In this work, a simple yet effective method for preparing a novel double-network hydrogel was reported. First, nonfouling polymer, poly(N-(2-hydroxyethyl)acrylamide) (PHEAA), was crosslinked through covalent bonds. Antibacterial polysaccharide, chitosan (CS), was then crosslinked by chelation between the N-glucosamine units on the CS and citrate or sulfate ions. The poly(N-(2-hydroxyethyl)acrylamide)/chitosan double-network hydrogels (PHEAA/CS DN hydrogels) exhibited high tensile strength (3.8 MPa), strong elastic modulus (0.6 MPa). And the dynamic ionic crosslinking in CS network provided the DN gels with fast self-recovery ability as well as excellent fatigue resistance. Furthermore, the mechanical properties of the DN gels were enhanced after stretching and relaxing because of the molecular orientation and reconstruction of chitosan network. More importantly, the hydrogels have excellent antifouling and antibacterial properties, which is called "repelling and killing", making them competitive candidates for applications in the biomedical field.

2.
ACS Appl Mater Interfaces ; 11(35): 31594-31604, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31407568

RESUMO

Because of their self-recovery ability and fatigue resistance, double-network (DN) hydrogels with hybrid ionical-covalent cross-linking have received wide attention. In this work, by a simple "one-pot" method, a novel kind of hybrid ionic-covalent chitosan/poly(sulfobetaine methacrylate) (CS/PSBMA) DN hydrogels was prepared. The hydrogels showed high tensile strength (2.0 MPa), strong elastic modulus (0.5 MPa), fast self-recovery ability as well as excellent fatigue resistance, high mechanical strength, and toughness retention rate after soaking in water for 24 h. Additionally, the mechanical properties of the DN gels were enhanced after stretch and relaxation because of the rearrangement of the CS network. More excitingly, because of the antifouling feature of PSBMA and the inherent antibacterial property of CS, the hybrid DN hydrogels demonstrated a "repel and kill" effect on microorganisms. The CS/PSBMA DN hydrogels may find potential applications in biomedical fields, such as artificial connective tissues, implantable devices, and wound dressing.

3.
Cell Metab ; 30(2): 319-328.e8, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31230984

RESUMO

Asprosin is a fasting-induced hormone that promotes glucose production in the liver and stimulates appetite in the hypothalamus by activating the cAMP signaling pathway via an unknown G protein-coupled receptor (GPCR). However, the bona fide receptor of Asprosin is unclear. Here, we have identified that the olfactory receptor OLFR734 acts as a receptor of Asprosin to modulate hepatic glucose production. Olfr734 knockout mice show a blunted response to Asprosin, including attenuated cAMP levels and hepatic glucose production, and improved insulin sensitivity. As Olfr734 deficiency dramatically attenuates both fasting and high-fat-diet-induced glucose production, our results demonstrate a critical role of OLFR734 as a receptor of Asprosin to maintain glucose homeostasis during fasting and in obesity.

4.
Cell Mol Biol Lett ; 24: 40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223315

RESUMO

Paclitaxel is a well-known anticancer agent with a unique mechanism of action. It is considered to be one of the most successful natural anticancer drugs available. This study summarizes the recent advances in our understanding of the sources, the anticancer mechanism, and the biosynthetic pathway of paclitaxel. With the advancement of biotechnology, improvements in endophytic fungal strains, and the use of recombination techniques and microbial fermentation engineering, the yield of extracted paclitaxel has increased significantly. Recently, paclitaxel has been found to play a large role in tumor immunity, and it has a great potential for use in many cancer treatments.


Assuntos
Biotecnologia/métodos , Imunoterapia , Neoplasias/terapia , Paclitaxel/uso terapêutico , Animais , Antineoplásicos Fitogênicos/biossíntese , Antineoplásicos Fitogênicos/uso terapêutico , Fermentação , Fungos/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Paclitaxel/biossíntese , Paclitaxel/farmacologia
5.
Langmuir ; 35(18): 6120-6128, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30983368

RESUMO

A dual-sensitive drug delivery system (DDS) based on graphene oxide (GO) which is simultaneously loaded with proapoptotic peptides and anticancer drugs was rationally designed and fabricated for cancer synergetic therapy. Specifically, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on the surface of GO via a disulfide bond to obtain GO-SS-KLA. Then, the aromatic anticancer drug doxorubicin (DOX) was loaded on GO through π-π conjugation and hydrogen bonding interactions. Finally, bovine serum albumin (BSA) was used to coat the GO carrier to obtain a biological medium-stable GO-based DDS, DOX@GO-SS-KLA/BSA. The results show that KLA and DOX can be released responding to the reductive and pH stimulus inside the cells, respectively, and achieve a synergetic therapy for cancer. Moreover, the results of stability studies show that DOX@GO-SS-KLA/BSA could be stably dispersed in water for more than 8 days and in 10% fetal bovine serum for at least 6 days. The constructed DOX@GO-SS-KLA/BSA exhibits great potential as a drug carrier for co-delivery of various therapeutic agents.

6.
Mol Cancer Ther ; 18(5): 886-899, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30926635

RESUMO

Nur77 (also called TR3 or NGFI-B), an orphan member of the nuclear receptor superfamily, induces apoptosis by translocating to mitochondria where it interacts with Bcl-2 to convert Bcl-2 from an antiapoptotic to a pro-apoptotic molecule. Nur77 posttranslational modification such as phosphorylation has been shown to induce Nur77 translocation from the nucleus to mitochondria. However, small molecules that can bind directly to Nur77 to trigger its mitochondrial localization and Bcl-2 interaction remain to be explored. Here, we report our identification and characterization of DIM-C-pPhCF3 +MeSO3 - (BI1071), an oxidized product derived from indole-3-carbinol metabolite, as a modulator of the Nur77-Bcl-2 apoptotic pathway. BI1071 binds Nur77 with high affinity, promotes Nur77 mitochondrial targeting and interaction with Bcl-2, and effectively induces apoptosis of cancer cells in a Nur77- and Bcl-2-dependent manner. Studies with animal model showed that BI1071 potently inhibited the growth of tumor cells in animals through its induction of apoptosis. Our results identify BI1071 as a novel Nur77-binding modulator of the Nur77-Bcl-2 apoptotic pathway, which may serve as a promising lead for treating cancers with overexpression of Bcl-2.

7.
J Vasc Surg ; 70(2): 547-553, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30850291

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the outcome and the factors associated with stenosis after treatment using partial aneurysmectomy for aneurysm in autologous arteriovenous fistulas. METHODS: This retrospective cohort study was conducted from July 2007 to June 2016 and included patients with complicated aneurysms in upper extremity autologous arteriovenous fistulas were treated by partial aneurysmectomy. Vascular ultrasound examination was performed every 6 months after the surgery. RESULTS: Forty-one patients (median age, 37 years; 70.7% males) were included. Of the patients, 95.1% had a radial-cephalic fistula in the forearm and nearly 88% had 1 or 2 aneurysms in arteriovenous fistulas that had been created for 10 to 84 months. Technical success of partial aneurysmectomy was achieved in all patients. The access diameter (44.0 ± 5.1 mm vs 10.4 ± 1.8 mm; P < .01) and brachial artery blood flow (1618.2 ± 277.0 mL/min vs 772.1 ± 127.4 mL/min; P < .01) were significantly decreased after the surgery. The median follow-up time was 27 months (range, 12-43 months). The primary patency rates at 6 and 12 months were 100% and 95%, respectively. Loss of patency was due to stenosis of the remodeled fistulas, which occurred in seven patients (17%). Multivariate COX regression analysis revealed that diabetes (hazard ratio, 114.28; 95% confidence interval, 2.85-4583.94; P = .01) was a risk factor for the impaired primary patency rates. A larger postprocedure residual diameter trended to favor fistula patency (hazard ratio, 0.46; P = .07). Stenosis was successfully treated with percutaneous transluminal angioplasty. CONCLUSIONS: Partial aneurysmectomy is an effective and safe method for treating aneurysm of upper extremity autologous arteriovenous fistulas, leading to good 12-month primary patency and no aneurysm recurrence. Using a larger catheter to size the revised fistula during aneurysmectomy may increase access patency.

8.
Protein Cell ; 10(8): 583-594, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30887444

RESUMO

A change in the metabolic flux of glucose from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis is regarded as one hallmark of cancer. However, the mechanisms underlying the metabolic switch between aerobic glycolysis and OXPHOS are unclear. Here we show that the M2 isoform of pyruvate kinase (PKM2), one of the rate-limiting enzymes in glycolysis, interacts with mitofusin 2 (MFN2), a key regulator of mitochondrial fusion, to promote mitochondrial fusion and OXPHOS, and attenuate glycolysis. mTOR increases the PKM2:MFN2 interaction by phosphorylating MFN2 and thereby modulates the effect of PKM2:MFN2 on glycolysis, mitochondrial fusion and OXPHOS. Thus, an mTOR-MFN2-PKM2 signaling axis couples glycolysis and OXPHOS to modulate cancer cell growth.

9.
Bioinformatics ; 35(17): 3199-3202, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668649

RESUMO

MOTIVATION: Numerous experimental and computational studies in the biomedical literature have provided considerable amounts of data on diverse RNA-RNA interactions (RRIs). However, few text mining systems for RRIs information extraction are available. RESULTS: RNA Interactome Scoper (RIscoper) represents the first tool for full-scale RNA interactome scanning and was developed for extracting RRIs from the literature based on the N-gram model. Notably, a reliable RRI corpus was integrated in RIscoper, and more than 13 300 manually curated sentences with RRI information were recruited. RIscoper allows users to upload full texts or abstracts, and provides an online search tool that is connected with PubMed (PMID and keyword input), and these capabilities are useful for biologists. RIscoper has a strong performance (90.4% precision and 93.9% recall), integrates natural language processing techniques and has a reliable RRI corpus. AVAILABILITY AND IMPLEMENTATION: The standalone software and web server of RIscoper are freely available at www.rna-society.org/riscoper/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

10.
Nat Prod Res ; : 1-5, 2019 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-30663383

RESUMO

A rapid PCR technology was developed to differentiate Cervus antlers species and adulteration based on the difference in mitochondrial genome. Three specifically designed primer sets were confirmed to have high inter-species specificity and good intra-species stability. Limits of detection were estimated to be 1 ng of genomes for reindeer and 10 ng for the other species. Especially, when the mixture of Cervus antlers and reindeer or sambar was assayed, these primer sets still exhibited strong capability of differentiation but not the conventional COI barcoding. By using the newly developed approach, five batches out of fourteen commercial Cervus antler products were identified to be fake products made from reindeer antlers. It has shown its good potential to be extensively applied in the identification of counterfeits or adulterates of Cornu Chinese medicines for their pulverized and processed form, and even the traditional Chinese patent medicines composed of these species.

11.
Plant J ; 98(1): 71-82, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30556198

RESUMO

Root hair, a special type of tubular-shaped cell, outgrows from the root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with biotic and abiotic stresses. Studies in the model plant Arabidopsis have revealed that root-hair initiation and elongation are hierarchically regulated by a group of basic helix-loop-helix (bHLH) transcription factors (TFs). However, knowledge regarding the regulatory pathways of these bHLH TFs in controlling root hair growth remains limited. In this study, RNA-seq analysis was conducted to profile the transcriptome in the elongating maize root hair and >1000 genes with preferential expression in root hair were identified. A consensus cis-element previously featured as the potential bHLH-TF binding sites was present in the regulatory regions for the majority of the root hair-preferentially expressed genes. In addition, an individual change in ZmLRL5, the highest-expressed bHLH-TF in maize root hair resulted in a dramatic reduction in the elongation of root hair, and rendered the growth of root hair hypersensitive to translational inhibition. Moreover, RNA-seq, yeast-one-hybrid and ribosome profile analysis suggested that ZmLRL5 may function as a key player in orchestrating the translational process by directly regulating the expression of translational processes/ribosomal genes during maize root hair growth.

12.
Colloids Surf B Biointerfaces ; 175: 65-72, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30522009

RESUMO

A multifunctional envelope-type mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Firstly, a kind of cell apoptosis peptide (KLAKLAK)2 (KLA) was anchored on surface of MSN via disulfide bond to obtain MSN-SS-KLA. Subsequently, anticancer drug doxorubicin hydrochloride (DOX) was loaded into the pores of MSN-SS-KLA. Then, the drug loaded MSN-SS-KLA (DOX@MSN-SS-KLA) was further coated with bovine serum albumin (BSA) to obtain a biological media stable MSN based drug delivery system (DDS), DOX@MSN-SS-KLA/BSA, for cancer synergetic therapy. The results show that stability of the DOX@MSN-SS-KLA/BSA is much better than that of DOX@MSN-SS-KLA and it could keep well dispersed in serum for more than 24 h. After accumulating at tumor site by EPR effect, the DOX@MSN-SS-KLA/BSA could be effectively phagocytosed by HeLa cells and release apoptotic peptide KLA as well as DOX simultaneously responding to reductive stimulus inside the cells. In vitro cell experiment results show that the DOX@MSN-SS-KLA/BSA complex exhibits much better inhibition on HeLa cells compared with pure DOX, indicating that co-delivery of KLA and DOX is expected to achieve synergetic therapy of cancer.

13.
Sensors (Basel) ; 18(11)2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30463382

RESUMO

The internet-of-things (also known as IoT) connects a large number of information-sensing devices to the Internet to collect all kinds of information needed in real time. The reliability of the source of a large number of accessed information tests the processing speed of signatures. Batch signature allows a signer to sign a group of messages at one time, and signatures' verification can be completed individually and independently. Therefore, batch signature is suitable for data integration authentication in IoT. An outstanding advantage of batch signature is that a signer is able to sign as many messages as possible at one time without worrying about the size of signed messages. To reduce complexity yielded by multiple message signing, a binary tree is usually leveraged in the construction of batch signature. However, this structure requires a batch residue, making the size of a batch signature (for a group of messages) even longer than the sum of single signatures. In this paper, we make use of the intersection method from lattice to propose a novel generic method for batch signature. We further combine our method with hash-and-sign paradigm and Fiat⁻Shamir transformation to propose new batch signature schemes. In our constructions, a batch signature does not need a batch residue, so that the size of the signature is relatively smaller. Our schemes are securely proved to be existential unforgeability against adaptive chosen message attacks under the small integer solution problem, which shows great potential resisting quantum computer attacks.

14.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 35(5): 822-828, 2018 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-30370726

RESUMO

Nuclear receptors are transcriptional regulators involved in almost all biological processes such as cell growth, differentiation, apoptosis, substance metabolism and tumor formation, and they can be regulated by small molecules that bind to them. Autophagy is a special way of programmed cell death and it is a highly conserved metabolic process. Once autophagy defects or excessive autophagy occur, the disease will develop. In recent years, numerous studies have shown that nuclear receptors are related to autophagy. Therefore, this paper mainly reviews the research progress on nuclear receptors involved in the regulation of autophagy, and focuses on the mechanism of several nuclear receptors involved in the regulation of autophagy, aiming at understanding the molecular basis of how nuclear receptors participate in regulating autophagy, as well as providing possible ideas and strategies for the treatment of corresponding diseases.

15.
Mol Med Rep ; 18(6): 4793-4801, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272297

RESUMO

Nuclear receptor subfamily 4 group A member 1 (NR4A1; also termed Nur77/TR3/NGFIB), a member of the nuclear receptor superfamily, is expressed as an early response gene to regulate the expression of multiple target genes. Nur77 has the typical structure of a nuclear receptor, including an N­terminal domain, a DNA binding domain, and a ligand­binding domain. The expression and localization of Nur77 are closely associated with its roles in cell proliferation and apoptosis. Nur77 was first identified as an orphan receptor, the endogenous ligand of which has not yet been identified; however, an increasing number of compounds targeting Nur77 have been reported to have beneficial effects in the treatment of cancer and other diseases. This review provides a brief overview of the identification, structure, expression and localization, transcriptional role and non­genomic function of Nur77, and summarizes the ligands that have been shown to interact with Nur77, including cytosporone B, cisplatin, TMPA, PDNPA, CCE9, THPN, Z­ligustilide, celastrol and bisindole methane compounds, which may potentially be used to treat cancer in humans.

16.
Genes Dis ; 5(2): 137-149, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30258943

RESUMO

Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney. Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases, which requires a thorough understanding of podocyte cell biology. As mature podocytes lose proliferative capacity, a conditionally SV40 mutant tsA58-immortalized mouse podocyte line (designated as tsPC) was established from the Immortomouse over 20 years ago. However, the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells. In this study, we establish a user-friendly and reversibly-immortalized mouse podocyte line (designated as imPOD), on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen, which is flanked with FRT sites. We show the imPOD cells exhibit long-term high proliferative activity, which can be effectively reversed by FLP recombinase. The imPOD cells express most podocyte-related markers, including WT-1, Nephrin, Tubulin and Vinculin, but not differentiation marker Synaptopodin. The imPOD cells do not form tumor-like masses in vivo. We further demonstrate that TGFß1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers, α-SMA, Vimentin and Nestin, as well as fibrogenic factors CTGF and Col1a1. Collectively, our results strongly demonstrate that the newly engineered imPOD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.

18.
Langmuir ; 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30089359

RESUMO

In this paper, a novel kind of zwitterion modified graphene oxide (GO) for promoting stability and reducing aggregation of GO as a drug carrier was proposed and demonstrated. Specifically, the GO was functionalized with a kind of zwitterion based silane, 3-(dimethyl(3-(trimethoxysilyl)propyl)-ammonio)propane-1-sulfonate (SBS). After zwitterion modification, the SBS functionalized GO (GO-SB) shows significantly enhanced stability in both serum-free and serum-containing solution, especially after loading doxorubicin hydrochloride (DOX). According to drug release profiles, the drug-loaded GO-SB exhibits thermosensitive and sustained release behavior. Meanwhile, in vitro studies show that the DOX loaded GO-SB could be easily internalized by HepG2 cells and exhibit obvious cytotoxicity on the cells. And, in vivo studies demonstrate that the GO-SB drug carrier is capable of being taken by the larvae of zebrafish and can be eliminated from the body within several days.

19.
Cell Mol Biol Lett ; 23: 36, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30093910

RESUMO

The nuclear receptor RXRα (retinoid X receptor-α) is a transcription factor that regulates the expression of multiple genes. Its non-genomic function is largely related to its structure, polymeric forms and modification. Previous research revealed that some non-genomic activity of RXRα occurs via formation of heterodimers with Nur77. RXRα-Nur77 heterodimers translocate from the nucleus to the mitochondria in response to certain apoptotic stimuli and this activity correlates with cell apoptosis. More recent studies revealed a significant role for truncated RXRα (tRXRα), which interacts with the p85α subunit of the PI3K/AKT signaling pathway, leading to enhanced activation of AKT and promoting cell growth in vitro and in animals. We recently reported on a series of NSAID sulindac analogs that can bind to tRXRα through a unique binding mechanism. We also identified one analog, K-80003, which can inhibit cancer cell growth by inducing tRXRα to form a tetramer, thus disrupting p85α-tRXRα interaction. This review analyzes the non-genomic effects of RXRα in normal and tumor cells, and discusses the functional differences based on RXRα protein structure (structure source: the RCSB Protein Data Bank).


Assuntos
Receptor X Retinoide alfa/química , Receptor X Retinoide alfa/metabolismo , Animais , Sítios de Ligação , Bases de Dados de Proteínas , Descoberta de Drogas , Humanos , Modelos Moleculares , Neoplasias/metabolismo , Conformação Proteica , Multimerização Proteica
20.
Sci Rep ; 8(1): 10988, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30030497

RESUMO

Chronic kidney disease (CKD) poses a formidable challenge for public healthcare worldwide as vast majority of patients with CKD are also at risk of accelerated cardiovascular disease and death. Renal fibrosis is the common manifestation of CKD that usually leads to end-stage renal disease although the molecular events leading to chronic renal fibrosis and eventually chronic renal failure remain to be fully understood. Nonetheless, emerging evidence suggests that an aberrant activation of PI3Kγ signaling may play an important role in regulating profibrotic phenotypes. Here, we investigate whether a blockade of PI3Kγ signaling exerts any beneficial effect on alleviating kidney injury and renal fibrosis. Using a mouse model of angiotensin II (Ang II)-induced renal damage, we demonstrate that PI3Kγ inhibitor AS605240 effectively mitigates Ang II-induced increases in serum creatinine and blood urea nitrogen, renal interstitial collagen deposition, the accumulation of ECM proteins and the expression of α-Sma and fibrosis-related genes in vivo. Mechanistically, we reveal that AS605240 effectively inhibits Ang II-induced cell proliferation and phosphorylation of Akt in fibroblast cells. Furthermore, we demonstrate that Ang II-upregulated expression of IL-6, Tnf-α, IL-1ß and Tgf-ß1 is significantly attenuated in the mice treated with AS605240. Taken together, our results demonstrate that PI3Kγ may function as a critical mediator of Ang II-induced renal injury and fibrosis. It is thus conceivable that targeted inhibition of PI3Kγ signaling may constitute a novel therapeutic approach to the clinical management of renal fibrosis, renal hypertension and/or CKD.

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